Abstract
Population-based studies identified an association between a prior pregnancy complicated by gestational diabetes mellitus (GDM) and cardiac hypertrophy and dysfunction later in life. It is however unclear whether GDM initiates this phenotype and what are the underlying mechanisms. We addressed these questions by using female rats that express human amylin (HIP rats) as a GDM model and their wild-type (WT) littermates as the normal pregnancy model. Pregnant and two months postpartum HIP females had increased left-ventricular mass and wall thickness compared to non-pregnant HIP females, which indicates the presence of concentric hypertrophy. These parameters were unchanged in WT females during both pregnancy and postpartum periods. Hypertrophic Ca2+-dependent calcineurin/NFAT signaling was stimulated two months after giving birth in HIP females but not in the WT. In contrast, the CaMKII/HDAC hypertrophy pathway was active immediately after giving birth and returned to the baseline by two months postpartum in both WT and HIP females. Myocytes from two months postpartum HIP females exhibited slower Ca2+ transient relaxation and higher diastolic Ca2+ levels, which may explain calcineurin activation. No such effects occurred in the WT. These results suggest that a GDM-complicated pregnancy accelerates the development of pathological cardiac remodeling likely through activation of calcineurin/NFAT signaling.
Document Type
Article
Publication Date
10-22-2021
Digital Object Identifier (DOI)
https://doi.org/10.1038/s41598-021-00422-3
Funding Information
This work was supported by the National Institutes of Health (Grant Numbers HL148443 and HL135000 to S.D., HL118474 to F.D.), American Heart Association (Grant Number 19TPA34850094 to S.D.) and the University of Kentucky Research Alliance for Reduction of Diabetes Associated Microvascular Dysfunction (ADAM).
Repository Citation
Verma, Nirmal; Srodulski, Sarah; Velmurugan, Sathya; Hoskins, Amanda; Pandey, Vivek K.; Despa, Florin; and Despa, Sanda, "Gestational Diabetes Triggers Postpartum Cardiac Hypertrophy via Activation of Calcineurin/NFAT Signaling" (2021). Pharmacology and Nutritional Sciences Faculty Publications. 123.
https://uknowledge.uky.edu/pharmacol_facpub/123
Supplementary information
Notes/Citation Information
Published in Scientific Reports, v. 11, issue 1, article no. 20926.
© 2021 The Author(s)
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